Due to the specific property of allowing simultaneous binding to at least two different antigens, multispecific antibodies, such as bispecific antibodies with two different antigen-recognition sites, have been expected to be developed as drugs or diagnostic agents. However, that has been impeded by low productivity and difficulties in purification, and there has been little progress towards practicalization.
Moreover, while there are several known methods for effectively producing multispecific antibodies, most attempt to effectively produce multispecific antibodies by restricting heavy chain-heavy chain bonds (Patent Documents 1-6).
Additionally, the disclosures of the following patent documents are all incorporated in the present specification by reference.
Patent Document 1: WO 98/50431
Patent Document 2: WO 2010/151792
Patent Document 3: U.S. Pat. No. 7,183,076
Patent Document 4: WO 2009/089004
Patent Document 5: WO 2007/147901
Patent Document 6: WO 2011/034605